A Phase 2, Double-blind, Active-controlled, Dose-titrating Efficacy and Safety Study of Firibastat Compared to Ramipril Administered Orally, Twice Daily, Over 12 Weeks to Prevent Left Ventricular Dysfunction After Acute MI
Overview
- Phase
- Phase 2
- Intervention
- Firibastat
- Conditions
- Myocardial Infarction
- Sponsor
- Quantum Genomics SA
- Enrollment
- 295
- Locations
- 7
- Primary Endpoint
- Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a multicenter, randomized, double-blind, active-controlled, dose-titrating phase 2 study to evaluate the safety and efficacy of firibastat administered orally BID (2 daily doses) versus ramipril administered orally BID over 12 weeks after acute anterior MI.
Subjects will be followed for 12 weeks (over 4 study visits). A total of 294 male and female subjects with a diagnosis of first acute anterior MI will be randomized. The subjects will need to have a primary percutaneous coronary intervention (PCI) of the index MI related artery within 24 hours after MI.
Detailed Description
At Inclusion Visit (Visit 2 \[within 72 hours after acute MI\]), subjects will be randomly assigned to 1 of the following 3 treatment groups in a 1:1:1 ratio: * Group 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks * Group 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks * Group 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks Then subjects will undergo study procedures at Titration Visit (Visit 3 \[Day 14\]), Treatment Visit (Visit 4 Day 42\]) and End-of-Treatment Visit (Visit 5 \[Day 84\]).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of first acute anterior MI (ST-elevation myocardial infarction) defined as chest pain \>30 minutes and ST elevation ≥0.2 mV in at least 2 consecutive electrocardiogram (ECG) leads in the anterior area (DI, aVL, V1 V6).
- •Primary PCI of the index-MI-related artery within 24 hours after the MI.
Exclusion Criteria
- •Body mass index \>45 kg/m².
- •Subject is hemodynamically unstable or has cardiogenic shock.
- •Subjects with clinical signs of HF (Kilipp III and IV).
- •Systolic blood pressure \<100 mmHg at inclusion visit
- •Early primary PCI of the index-MI-related artery performed within 3 hours after MI.
- •Subjects treated with angiotensin-converting-enzyme inhibitor (ACE I), angiotensin receptor blocker (ARB) or sacubitril/valsartan prior to the index magnetic resonance imaging. Note: if treatment was for HTN, ACE I/ARB should be stopped, and, if necessary, another therapeutic class can be prescribed for HTN. If the ACE I/ARB was prescribed for congestive HF, the subject is not considered eligible; if the ACE I/ARB prescribed for another reason cannot be stopped, the subject is not eligible for study inclusion.
- •Subjects scheduled for implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy, or pacemaker within the next 3 months. If an ICD is indicated for ventricular arrhythmia during the course of the study, a life vest, when possible, should be prescribed and the ICD scheduled after study completion.
Arms & Interventions
Group 1: firibastat 100 mg
Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.
Intervention: Firibastat
Group 2: firibastat 500 mg
Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.
Intervention: Firibastat
Group 3: ramipril 5 mg
Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.
Intervention: Ramipril
Outcomes
Primary Outcomes
Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)
Time Frame: 84 days
Comparison of the effects of BID oral administration of 2 doses of firibastat to those of BID oral administration of ramipril on the change from Baseline in LVEF on Day 84
Secondary Outcomes
- N-terminal Pro B-type Natriuretic Peptide (NT proBNP)(84 days)
- Left-ventricle End-systolic Volume Assessed by CMRI(84 days)
- Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization(84 days)
- Left-ventricle End-diastolic Volume Assessed by CMRI(84 days)